This program project will investigate changes in cerebral function in aging using both animal and human subjects. The issue of normal versus pathologic cerebral changes with aging will be particularly explored. Brain tissue slices will be used to study carbohydrate and amino acid metabolism and neurotransmitters in young and old mice. Energy sources will be used to locate defective sites in the metabolic pathways. Kindling and frequency potentiation studies will be used in young and old rats to clarify changes in neuroplasticity with aging. Cognitive, electroencephalographic, and evoked potential studies will be used in a geriatric clinical population both without and with dementia to identify changes associated with age and with cerebral atrophy as identified by computerized tomography. Longitudinal studies will demonstrate ongoing changes and point out important prognostic predicters.